Ocular melanoma refers to two distinct diseases, uveal and conjunctival melanoma, which differ significantly in epidemiological aspects.
The average annual incidence of uveal and conjunctival melanoma is 5-6 and 0.6-0.8 per million people, respectively. Approximately 6679-7095 uveal and 1381-1618 conjunctival melanomas are diagnosed annually, and for each new patient at least 13-15 survivors are alive.
The incidence of ocular melanoma varies widely according to age, ethnicity and latitude. Most new cases are diagnosed between 45 and 80 years of age. Non-Hispanic white Caucasians have the highest incidence of uveal and conjunctival melanoma, 5.5-6.0 and 0.5-0.8 per million, respectively. The corresponding incidences are lowest in people of African and Asian origin, 0.2-0.4 and 0.15-0.18 per million, respectively.
The incidence of conjunctival melanoma increases with more UV radiation from 0.3 to 0.9 per million from high to low latitudes, whereas the reverse is true of uveal melanoma, which increases in incidence from 1.4 to 8.6 per million toward high latitudes.
Germline mutations of BAP1, which predisposes to several cancers, are an infrequent but important cause of familial uveal melanoma. The most important precursors of uveal melanoma are uveal nevi and congenital ocular and oculodermal melanocytosis, which carry a 1:400-1:500 lifetime risk of uveal melanoma. Primary acquired melanosis of the conjunctiva carries an even higher risk of conjunctival melanoma developing.
Conjunctival naevi are common lesions of the conjunctival epithelium and substantia propria. They are classified as either congenital or acquired, and usually develop during the first decade of life. Acquired naevi are typically located near the limbus, and may drape over the peripheral cornea. They rarely require excision, except where rapid growth or irritative symptoms are present. However they are cosmetically disfiguring.
“Inflamed naevi of puberty and young adulthood,” as termed by Folberg and colleagues in their review of benign conjunctival melanocytic lesions, are conjunctival naevi that seem to be enlarging and are histologically associated with extensive inflammatory infiltrate.
Conjunctival melanocytic tumors comprise benign and malignant neoplasms.
Nevi are congenital benign melanocytic tumors that can be further classified into junctional, subepithelial, compound, and blue nevus as well as congenital melanocytosis. In the text, the term “nevus” refers to the most common form of nevi, the compound nevus (a nevus with a junctional and a subepithelial component).
Primary acquired melanosis (PAM) can either be regarded as benign (PAM without atypia) or represent a precancerous lesion (PAM with atypia), whereas a melanoma is per definition a malignant melanocytic tumor.
Nevi exhibit usually cysts (that can be detected on slit lamp examination and with sonography/anterior segment OCT) and are reported by the patient to exist for a long time (as they are often congenital).
Malignant melanomas can start as a nevus/freckle or arise as newly formed conjunctival pigmentation called primary acquired melanosis (PAM).
A simple biopsy can determine whether a pigmented conjunctival tumor is a nevus, primary acquired melanosis, or conjunctival melanoma. A biopsy is not a desirable procedure for anyone to undergo. It carries the risk of aggravating the growth of the lesion.
A nevus of the conjunctiva does not typically grow (except at puberty). They do not usually extend onto the cornea or develop large feeder blood vessels.
Pigmented conjunctival tumors that are raised, hypervascular, or extend onto the cornea are considered suspicious. Though suspicious conjunctival tumors can be biopsied after a first visit to the eye cancer specialist, close observation for evidence of growth (prior to biopsy) may also be recommended. Documented tumor growth is a strong indicator that biopsy should be performed.
A pigmented conjunctival nevus can be photographed and followed for evidence of growth prior to biopsy or excision. It is important to note that both benign and malignant tumors can grow (though malignant tumors will grow faster). Nevus are not expected to disappear spontaneously.
The predominant benign conjunctival melanocytic lesions are composed of a variety of nevi and melanosis that have a predilection for the perilimbal bulbar conjunctiva. Nevi are believed to be congenital lesions that are generally unilateral. They are usually first identified in early adulthood, they frequently develop cysts and become slightly elevated and may change in color and size. Dark brown melanotic pigmentation is normally observed in the conjunctiva, a condition referred to a racial melanosis, which is evident bilaterally form an early age in more pigmented races. This condition is usually caused by an excess production of melanin or hyperpigmentation by the melanocytes (forming an ephelis) or benign proliferation of melanocytes (forming a benign lentigo).
The terminology associated with melanosis is controversial, especially when melanosis is unilateral and acquired, in that case lesion can be a precursor of invasive melanoma. Some authors referred this unilateral acquired pigmentation as a precancerous melanosis, which in the past has led to an inappropriate aggressive therapy—frequently exenteration of the orbit (surgical excision of the orbital contents—the eyeglobe, muscles, and eyelids, too.) As a result, others have referred these lesions as benign acquired melanosis, but this terminology has caused concern that the malignant potential of this condition may be overlooked. Because these lesions may show variable histological findings, WHO proposed the term primary acquired melanosis (PAM) with or without atypia for these lesions.
Conjunctival melanoma is relatively rare condition, occurring only in 1/40th compared to choroidal melanoma and approximately 500 times less often than cutaneous melanoma. Its incidence is 0.2 to 0.8 per million in white population. Conjunctival melanoma is a potentially lethal neoplasm, with an average 10 year mortality rate of 30%. It is identified most frequently in the perilimbal interpalpebral bulbar conjunctiva with tumor masses located in the palpebral or fornical conjunctiva or caruncle, plica semilunaris or eyelid margins having a worse prognosis for survival. Conjunctival melanoma has no sexual predilection, and it is found predominantly in middle-aged adults. This disease occurs mainly in white population, with rare reports in black on other populations. Recent studies have indicated that the incidence of epibulbar melanoma is increasing similarly to cutaneous melanoma.
Conjunctival melanomas are malignant tumors of proliferating melanocytes that are derived from the neural crest. The conjunctiva is a mucous membrane covering the anterior half of the pericorneal globe (bulbar conjunctiva) and lining the posterior surface of the eyelids (palpebral conjunctiva) forming a fold in the superior and inferior fornices (forniceal conjunctiva). Since the conjunctival stroma (the substantia propria) contains blood vessels and lymphatic vessels, a malignancy that invades the subepithelial region has a potential for local and systemic metastases.
The aim of the treatment is to reduce the opportunity for spreading the tumor mass. Dissemination can be done by local extension and by spread into the regional lymphatic nodes (ipsilateral, preauricular and submandibular lymph nodes), which are the most common site for metastasis. The mortality rate is over 5%. When tumor arises from PAM, the mortality rate increases to 40%.
Other indicators of a poor prognosis are involvement of the palpebral conjunctiva, fornixal conjunctiva or caruncle, severe cellular atypia, invasion into deeper ocular tissues, greater than 5 mitotic figures per high-power field, lack of an induced inflammatory response.
A cataract is a clouding of the lens in the eye leading to a decrease in vision. Cataracts may affect one or both eyes. Often they develop slowly. Symptoms may include faded colors, blurry vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Poor vision may also result in an increased risk of falling and depression. Cataracts are the cause of half of blindness and 33% of visual impairment worldwide.
Cataracts are most commonly due to aging, but may also occur due to trauma, radiation exposure, be present from birth, or occur following eye surgery for other problems. Risk factors include diabetes, smoking tobacco, prolonged exposure to sunlight, and alcohol. Either clumps of protein or yellow-brown pigment may be deposited in the lens reducing the transmission of light to the retina at the back of the eye. Diagnosis is by an eye exam.
Clinical staging of senile cataract is based largely on the visual acuity of the patient, as follows:
Mature cataract—Patient cannot read better than 20/200 on the visual acuity chart
Immature cataract—Patient can distinguish letters at lines better than 20/200
Incipient cataract—Patient can still read at 20/20 but possesses a lens opacity as confirmed by slit lamp examination
Prevention includes wearing sunglasses and not smoking. Early on the symptoms may be improved with eyeglasses. If this does not help surgery to remove the cloudy lens and replace it with an artificial lens is the only effective treatment. Surgery is only needed if the cataracts are causing problems. Surgery generally results in an improved quality of life. Cataract surgery is not easily available in many countries. This is especially true for women.
About 20 million people globally are blind due to cataracts. It is the cause of about 5% of blindness in the United States and nearly 60% of blindness in parts of Africa and South America. Blindness from cataracts occurs in about 10 to 40 per 100,000 children in the developing world and 1 to 4 per 100,000 children in the developed world. Cataracts become more common with age. About half of people in the United States have had cataracts by the age of 80.